title: Phase II study of panitumumab, oxaliplatin, 5-fluorouracil, and concurrent radiotherapy as preoperative treatment in high-risk locally advanced rectal cancer patients (StarPan/STAR-02 Study).
abstract: BACKGROUND
  The aim of this phase II study was to assess the activity of panitumumab in combination with oxaliplatin, 5-fluorouracil, and external radiotherapy (RT) as preoperative treatment in locally advanced rectal cancer patients.
  
  
  METHODS
  Patients had rectal adenocarcinoma, cT3N+ or cT4N-/+ stage, located <12 cm from the anal margin. Panitumumab was administered before the start of chemo-RT, and every 2 weeks in combination with 5-fluorouracil-oxaliplatin with concurrent RT. Rectal surgery was carried out 7-8 weeks after the end of neoadjuvant treatment. The primary end point was a pathological complete response rate of 25%.
  
  
  RESULTS
  Sixty patients were enrolled from February 2007 to October 2009. Fifty-five (91.7%) patients underwent surgery. Rate of pathological complete response was 21.1% (95% confidence interval 10.4% to 31.6%). Pathological downstaging occurred in 33 of 57 (57.9%) patients. Grade 3-4 toxicity during neoadjuvant treatment was diarrhea (38.9%), cutaneous reactions (18.6%), nausea (5.1%), asthenia (3.4%), anorexia (3.4%), and neutropenia (1.7%). One toxic death was observed for diarrhea.
  
  
  CONCLUSIONS
  In our study, the primary end point is not reached and panitumumab combination treatment was associated with high incidence of grade 3-4 diarrhea. The higher pathological complete response rate in comparison with the results of previous neoadjuvant rectal cancer trials with anti-epidermal growth factor receptor monoclonal antibodies supports further studies necessary to understand the possibility of optimal regimens and sequences with chemo-RT.
authors.affiliation: Medical Oncology Unit, S. Orsola-Malpighi Hospital, Bologna. Electronic address: carmine.pinto@aosp.bo.it.
authors.forename: C
authors.initials: C
authors.lastname: Pinto
authors.affiliation: Medical Oncology Unit, S. Orsola-Malpighi Hospital, Bologna.
authors.forename: F
authors.initials: F
authors.lastname: Di Fabio
authors.affiliation: Medical Oncology Unit, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo.
authors.forename: E
authors.initials: E
authors.lastname: Maiello
authors.affiliation: Medical Oncology Unit, S. Orsola-Malpighi Hospital, Bologna.
authors.forename: S
authors.initials: S
authors.lastname: Pini
authors.affiliation: Medical Oncology Unit, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo.
authors.forename: T
authors.initials: T
authors.lastname: Latiano
authors.affiliation: Department of Medical Oncology, National Cancer Institute, Genoa.
authors.forename: C
authors.initials: C
authors.lastname: Aschele
authors.affiliation: Department of Medical Oncology, Regina Elena Cancer Institute, Rome.
authors.forename: C
authors.initials: C
authors.lastname: Garufi
authors.affiliation: Medical Oncology Unit, CROB, Rionero in Vulture.
authors.forename: A
authors.initials: A
authors.lastname: Bochicchio
authors.affiliation: Medical Oncology Unit, S. Carlo Hospital, Potenza.
authors.forename: G
authors.initials: G
authors.lastname: Rosati
authors.affiliation: Medical Oncology Unit, SM Misericordia Hospital, Udine.
authors.forename: G
authors.initials: G
authors.lastname: Aprile
authors.affiliation: Medical Oncology Unit, S. Orsola-Malpighi Hospital, Bologna.
authors.forename: S
authors.initials: S
authors.lastname: Giaquinta
authors.affiliation: Oncology Department, Mario Negri Institute, Milan.
authors.forename: V
authors.initials: V
authors.lastname: Torri
authors.affiliation: Laboratory of Molecular Genetics, Institute for Cancer Research and Treatment, University of Turin Medical School, Candiolo, Turin.
authors.forename: A
authors.initials: A
authors.lastname: Bardelli
authors.affiliation: Centre for the Study of Biological Markers of Malignancy, General Regional Hospital, Venice, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Gion
authors.affiliation: Medical Oncology Unit, S. Orsola-Malpighi Hospital, Bologna.
authors.forename: A
authors.initials: A
authors.lastname: Martoni
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000532:radiotherapy* / Q000601:surgery; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics; D003967:Diarrhea / Q000139:chemically induced; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D020360:Neoadjuvant Therapy; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D000077150:Oxaliplatin; D000077544:Panitumumab; D049268:Positron-Emission Tomography; D011300:Preoperative Care; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000532:radiotherapy* / Q000601:surgery
chemical_list: D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000077544:Panitumumab; D005472:Fluorouracil